Brief Summary We describe a patient with two recent episodes of tenofovir disoproxil fumarate (TDF)-associated acute kidney injury and six-class drug-resistant HIV infection who achieved and maintained viral suppression without worsening kidney function on a regimen including tenofovir alafenamide (TAF) through 48 weeks of therapy. The safety and efficacy of TAF in patients with TDF-associated renal tubulopathy and multiple drug resistance HIV has not yet been described. TAF may represent a useful option to maximally suppress HIV in patients with these complications.

Background. HIV protease inhibitors exhibit concentration-dependent viral inhibition. Higher once daily doses of darunavir boosted with ritonavir (DRV/r) may achieve viral suppression in place of twice daily dosing. International antiretroviral adherence guidelines recommend once daily regimens whenever possible. We present data on virologic suppression achieved with DRV 1,200 mg and ritonavir 100 mg once daily compared to approved DRV regimens. Methods. This retrospective observational study included all patients treated with DRV after documented use of another protease inhibitor at an urban immunodeficiency clinic. Data collection from inception of DRV use in August 2006 through March 2012 included patient demographics, viral loads, CD4+ cell counts, and resistance test results. The primary outcome of virologic suppression was defined as <50 copies/mL at 24 weeks. Differences in baseline characteristics and virologic outcomes across dosing groups were analyzed via one-way analysis of variance. Results. One hundred and thirty-five patients were included in the ITT analysis. Most patients had no known DRV RAMs at baseline. Virologic suppression rate was not different among treatment groups: 53.6% of patients on 1,200 mg daily, 52.3% on 600 mg twice daily, and 42.9% on 800 mg daily (P = 0.568). Conclusions. Darunavir 1,200 mg daily should be investigated for use in protease inhibitor-experienced patients.

4210 Introduction: Patients with HIV/AIDS are at high risk for developing oncologic diseases such as lymphomas. Since the mid-1990s, the implementation of combined antiretroviral therapy (cART) has decreased the incidence of AIDS-defining malignancies; however, the advent of chronic, controlled HIV infection has increased the incidence of non-AIDS-defining malignancies such as Hodgkin Lymphoma (HL). Mortality from HL and non-Hodgkin Lymphoma (NHL) has decreased with the addition of cART to traditional and dose-adjusted chemotherapy regimens. Many antiretroviral agents affect the metabolism of antineoplastic agents via cytochrome P450 interactions. Possible complications include decreased efficacy of antineoplastic agents and increased toxicity of either or both classes of drugs. Protease inhibitors, especially ritonavir, are potent CYP3A4 inhibitors and therefore have the potential to significantly increase toxicity of multiple antineoplastic agents. Excess neutropenia has been observed in prospective studies in concomitantly treated patients when protease inhibitors are included in cART. Despite this, there is currently no clear evidence to guide clinicians on how to dose pharmacologic agents to treat HIV/AIDS and lymphoma simultaneously. The purpose of this retrospective chart review was to evaluate the significance of the drug-drug interactions experienced by HIV/AIDS patients who were treated with antiretroviral agents and high-intensity chemotherapy for lymphoma. Methods: All patients treated at Hennepin County Medical Center from 1999–2010 were screened for the diagnoses of lymphoma and HIV/AIDS. Patients were included if they met the following criteria: age greater than 18 years; diagnosis of HIV or AIDS; diagnosis of lymphoma; and treatment with an antineoplastic regimen for lymphoma with concomitant antiretroviral therapy. Electronic medical records were systematically reviewed for patient demographics, CD4 counts, viral loads, complete blood counts, complete metabolic panels, planned chemotherapy regimens, and chemotherapy administration and discontinuation. Chemotherapy adverse drug reactions (ADRs) were recorded and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Medication profiles for each patient were screened for potential drug interactions. The primary outcomes were incidence of chemotherapy interruptions or changes due to toxicity and the time to such regimen changes. The secondary outcomes were the number of ADRs reported and the management of these events. Results: A total of 114 patients were identified as having both an HIV/AIDS diagnosis and an oncologic diagnosis, 31 of which were lymphomas. Eleven of the 31 patients received concomitant antiretroviral therapy and had medical records available for review, encompassing 7 chemotherapy regimens and 12 chemotherapy courses. Median age was 46 years and 9 of the patients were male. All chemotherapy courses were subject to potential drug-drug interactions with patients' cART with 10 courses potentially affected by the use of protease inhibitors in 9 patients. Delay or interruption due to chemotherapy toxicity occurred in 11 of 12 chemotherapy courses affecting 10 patients as early as before the completion of their first chemotherapy cycle and as late as their last chemotherapy cycle. The 11 patients experienced a total of 124 documented ADRs (16 grade III-V), and 10 patients had a total of 20 emergency department visits. Eight patients required hospitalization 16 times for management of their ADRs. One patient with Castleman disease died of cytokine release syndrome in spite of chemotherapy. Conclusion: Chemotherapy interruptions and delays may be common in the setting of concomitant antineoplastic and antiretroviral therapy for treatment of lymphoma and HIV/AIDS. Although most chemotherapy ADRs were grade I or II, concomitant cART may have contributed to the increased hospitalization rate of these patients. Further investigation is required to determine if risk-mitigation strategies such as chemotherapy dose-reduction, avoidance of cART regimens which include protease inhibitors, and therapeutic drug monitoring should be implemented. Disclosures: No relevant conflicts of interest to declare.